The goal of this project is to determine the molecular properties of the proenzyme factor XI and its activate product, factor XIa, so that it is possible to understand what molecular changes occur during activation and how they are related to biologic activity. Highly purified human factor XI will be prepared and labelled with 125I. Activated factor XI will be formed by either tryptic cleavage or reaction with factor XII and high molecular weight kininogen. Experiments using these reagents will clarify how much proteolytic cleavage is compatible with retention of biologic activity, define some of the properties of the substituent chains of maximally activated factor XI, determine how the proenzyme and active enzyme adsorb to and interact with surfaces and other proteins. Techniques to be used include SDS-polyacrylamide gel electrophoresis, gradient gel electrophoresis, isoelectric focusing, and chemical modification of factors XI and XIa.